Medical uses

Benign prostatic hyperplasia

Physicians use finasteride for the treatment of BPH, informally known as an enlarged prostate. The FDA-approved dose is 5 mg once a day. Six months or more of treatment with finasteride may be required to determine the therapeutic results of treatment. If the drug is discontinued, any therapeutic benefits reverse within about 6–8 months. Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start of urination, and decreased urinary flow.[1][2]

Male pattern baldness

Finasteride is used to treat male pattern hair loss (androgenetic alopecia) in men only.[3] Treatment provides about 30% improvement in hair loss after six months of treatment, and effectiveness only persists as long as the drug is taken.[4]

Contraindications

Adverse effects

Adverse effects from finasteride are rare.[6] The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA, which could mask the development of prostate cancer.[7][8]

Although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not increased, there are post-marketing reports of breast cancer in association with its use. Available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.[9][3]

The effect of finasteride on sexual function is controversial. A 2014 review found it did not differ from placebo in rates of sexual dysfunction.[4][10] However another review from 2014 found increased risks of impotence, erectile dysfunction, decreased libido, and ejaculation disorder when used for benign prostatic hyperplasia and androgenic alopecia.[11] There are case reports of persistent diminished libido or erectile dysfunction after stopping the drug and the FDA has updated the label to inform healthcare professionals of these reports.[4][12]

While depression is not a significant side effect,[1] a few small studies have suggested a possible connection.[13]

Mechanism of action

Finasteride is a 5-alpha-reductase inhibitor, specifically the type IIisoenzyme.[14] By inhibiting 5a-reductase, finasteride prevents conversion of testosterone to dihydrotestosterone (DHT) by the type II isoenzyme, resulting in a decrease in serum DHT levels by about 65–70% and in prostate DHT levels by up to 85–90%,[15] where expression of the type II isoenzyme dominates. Unlike dual inhibitors of both isoenzymes of 5α-reductase which can reduce DHT levels in the entire body by more than 99%, finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with 100-fold less affinity for I as compared to II.[3] In addition to blocking the type II isoenzyme, finasteride competitively inhibits the 5β-reductase type II isoenzyme,[16] though this is not believed to affect androgen metabolism.

By blocking DHT production, finasteride reduces androgen activity in the scalp. In the prostate, inhibition of 5α-reductase reduces prostate volume, which improves BPH and reduces risk of prostate cancer. 5α-Reductase inhibition also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[17]

DHT helps activate the GABAA receptor, which functions to tamp down signaling among neurons; because finasteride prevents the formation of DHT, it may contribute to a reduction of GABAA activity. Reduced GABAA has been implicated in depression, anxiety, and sexual dysfunction.[18][19][20]

Physical and chemical properties

Drug trade names include Propecia and Proscar, the former marketed for male pattern baldness (MPB) and the latter for benign prostatic hyperplasia (BPH), both are products of Merck & Co. There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride for the treatment of BPH expired on June 19, 2006.[22] Merck was awarded a separate patent for the use of finasteride to treat MPB. This patent expired in November 2013.[23]

History

In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of intersex children in the Caribbean who appeared sexually ambiguous at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic after onset of puberty. Her research group found these children shared a genetic mutation, causing deficiency of the 5α-reductase enzyme and male hormone dihydrotestosterone (DHT), which was found to have been the etiology behind abnormalities in male sexual development. Upon maturation, these individuals were observed to have smaller prostates which were underdeveloped, and were also observed to lack incidence of male pattern baldness.[24][25]

In 1975, copies of Imperato-McGinley's presentation were seen by P. Roy Vagelos, who was then serving as Merck's basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the condition found in these children to treat older men who were suffering from benign prostatic hyperplasia.[26]

In 2012, an advocacy group called the Post-Finasteride Syndrome Foundation was formed; the group "coined the phrase 'post finasteride syndrome' which they say is characterised by sexual, neurological, hormonal and psychological side effects that can persist in men who have taken finasteride for hair loss or an enlarged prostate".[30][31]

Research

Finasteride has been clinically tested for baldness in women; the results were no better than placebo.[32]